(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-ol → HCID 89754809, compound
Reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH:10]([C:12]([OH:15])([CH3:14])[CH3:13])[CH2:9][N:8]3[CH:16]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[N:18]=[C:7]3[C:6]=2[CH:23]=1.[CH3:24][C:25]1[O:29][N:28]=[C:27]([C@:30]([OH:34])([C:32]#[CH:33])[CH3:31])[CH:26]=1>>[OH:34][C@:30]([C:27]1[CH:26]=[C:25]([CH3:24])[O:29][N:28]=1)([CH3:31])[C:32]#[C:33][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH:10]([C:12]([OH:15])([CH3:14])[CH3:13])[CH2:9][N:8]3[CH:16]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[N:18]=[C:7]3[C:6]=2[CH:23]=1Participants
Procedure
Similar to as described in General Procedure G, racemic methyl 10-bromo-6-(2-hydroxypropan-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate was reacted with (2R)-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol to give methyl 10-((R)-3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-6-(2-hydroxypropan-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate. M+1=452. A solution of the above compound (100 mg, 0.22 mmol, 1.00 equiv) in methanol (Saturated with ammonia, 20 mL) was stirred for 3 days at 60° C. The resulting mixture was concentrated under vacuum. The residue was purified on a silica gel column with dichloromethane/methanol (19:1) to give a mixture of diastereoisomers. The two diasteromers were separated by Chiral-Prep-HPLC with the following conditions (Prep-HPLC-004): Column, Chiralpak IC, 2*25 cm, 5 um; mobile phase, Hex and ethanol (hold 40.0% ethanol in 25 min); Detector, UV 254/220 nm to give 12.2 mg (13%) Compound 1 as a off-white solid, Chiralpak IC-3, 25° C., 254 nm, 60:40 Hex (0.1% TEA):EtOH, 1 mL/min, tR=2,7 min; and 11.5 mg (12%) of Compound 2 as an off-white solid, Chiralpak IC-3, 25° C., 254 nm, 60:40 Hex (0.1% TEA):EtOH, 1 mL/min, tR=5.0 min.
Sources & evidence
- ORD record
- ord-8d81c8ec6425424c9ed121ca2b43a959
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034866B2
Reaction notes
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